The effectiveness of cytoreductive nephrectomy as a standard of care for untreated patients with metastatic renal cell carcinoma (mRCC) has been drawn into question with the introduction of targeted therapies. In some situations, it may be appropriate to delay surgery until after the administration of a targeted therapy, although surgery is generally the frontline standard, suggests Robert A. Figlin, MD.

Cytoreductive therapy should be administered upfront for patients with resectable disease who have uncontrollable pain, hematuria, or a paraneoplastic syndromes, believes Sumanta Kumar Pal, MD. In a SEER database analysis, patients who underwent cytoreductive nephrectomy experienced longer durations of disease-specific survival than those receiving targeted therapies.

In a similar analysis conducted by the International mRCC Database Consortium, overall survival was extended by cytoreductive surgery, specifically in patients with fewer than 3 risk factors and an expected lifespan greater than 12 months. Results from the phase III randomized CARMENA and SURTIME studies are needed before one approach can be declared superior, Pal believes. These studies are exploring surgery followed by sunitinib compared with sunitinib followed by surgery for patients with mRCC.

Surgery can be delayed for patients with a poor performance status, hypoalbuminemia, and excessive weight loss, suggests Daniel J. George, MD. These patients could benefit from treatment with temsirolimus, as a standard therapy for patients with poor-risk factors. The question of whether upfront temsirolimus or cytoreductive surgery is superior remains unanswered in randomized trials, George notes.

Frontline targeted therapies can be utilized for patients with borderline resectable disease with inferior vena cava involvement, notes George. In some situations, frontline therapies may downstage the patient to the point where resection is plausible. Additionally, patients with extensive metastatic disease and CNS involvement can delay surgery until after frontline treatment with targeted therapies, George states.

Patients with borderline resectable disease should be referred to highly experienced surgeons for the most optimal outcomes, George believes. Moreover, if the first-line therapy is unclear, referral to a tertiary care center that can provide multidisciplinary care is advised.